DESCRIPTION: (Applicant's Abstract) The function of nicotinic acetylcholine receptors (nAChRs) in the central nervous system (CNS), remains elusive. Complex dynamics of nicotine addiction and the extensive distribution of nAChRs in the brain suggests that they play important and varied roles. The purpose of the current proposal is to examine the contribution of nAChRs that bind the snake venom toxin, alpha-bungarotoxin (alphaBgt-AChRs), to excitability in CNS. The septo-hippocampal system provides extensive cholinergic inputs as well as a rich source of these receptors. An intact septo-hippocampal preparation will be used to look for evidence of endogenous alphaBgt-AChR activation in the hippocampus? This will entail the use of patchclamp and biophysical techniques to look for possible mediation of synaptic transmission by alphaBgt-AChRs as well as activation of the receptors by asynaptic release of agonist. The second part will involve examining the temporal and spatial properties of intracellular rise in calcium, by the activation of alphaBgt-AChRs, determined using fluorescence confocal microscopy. Further, the role of calcium dependent second messengers induced, and their impact on signaling by NMDA receptors present on the same postsynaptic cell will be investigated using biochemical techniques. These studies will provide valuable clues on the role of nicotinic receptors in synaptic signaling and plasticity in the mammalian brain and provide a mechanistic basis for the actions of nicotine.